PDBsum entry 4jq2

Oxidoreductase/oxidoreductase inhibitor

PDB id: 4jq2

Contents

Protein chains

316 a.a.

Ligands

SUZ

NAP ×2

EDO ×5

TLA

PO4

Waters ×332

PDB id:

4jq2

Name:

Oxidoreductase/oxidoreductase inhibitor

Title:

Akr1c2 complex with sulindac

Structure:

Aldo-keto reductase family 1 member c2. Chain: a, b. Synonym: 3-alpha-hsd3, chlordecone reductase homolog hakrd, dihydrodiol dehydrogenase 2, dd-2, dd2, dihydrodiol dehydrogenase/bile acid-binding protein, dd/babp, trans-1,2- dihydrobenzene-1,2-diol dehydrogenase, type iii 3-alpha- hydroxysteroid dehydrogenase. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: akr1c2, ddh2. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Resolution:

1.75Å R-factor: 0.166 R-free: 0.223

Authors:

Y.Yosaatmadja,J.U.Flanagan,C.J.Squire

Key ref:

Y.Yosaatmadja et al. Structural basis of nsaid selectivity for the aldo-Ke reductase 1c family. To be published, .

Date:

19-Mar-13 Release date: 02-Apr-14

Protein chains

P52895  (AK1C2_HUMAN) -  Aldo-keto reductase family 1 member C2 from Homo sapiens

Seq: 323 a.a.

Struc: 316 a.a.

Enzyme reactions

• Enzyme class 1: E.C.1.-.-.-
• Enzyme class 2: E.C.1.1.1.112 - indanol dehydrogenase.
• Reaction:
  1. (S)-indan-1-ol + NAD⁺ = indan-1-one + NADH + H⁺
  2. (S)-indan-1-ol + NADP⁺ = indan-1-one + NADPH + H⁺

(S)-indan-1-ol + NAD(+) (Bound ligand (Het Group name = NAP) matches with 91.67% similarity) = indan-1-one + NADH + H(+)

(S)-indan-1-ol + NADP(+) (Bound ligand (Het Group name = NAP) corresponds exactly) = indan-1-one + NADPH + H(+)

• Enzyme class 3: E.C.1.1.1.209 - 3(or 17)alpha-hydroxysteroid dehydrogenase.
• Reaction:
  1. androsterone + NADP⁺ = 5alpha-androstan-3,17-dione + NADPH + H⁺
  2. androsterone + NAD⁺ = 5alpha-androstan-3,17-dione + NADH + H⁺

androsterone (Bound ligand (Het Group name = SUZ) matches with 70.37% similarity) + NADP(+) (Bound ligand (Het Group name = NAP) corresponds exactly) = 5alpha-androstan-3,17-dione + NADPH + H(+)

androsterone (Bound ligand (Het Group name = SUZ) matches with 70.37% similarity) + NAD(+) (Bound ligand (Het Group name = NAP) matches with 91.67% similarity) = 5alpha-androstan-3,17-dione + NADH + H(+)

• Enzyme class 4: E.C.1.1.1.357 - 3alpha-hydroxysteroid 3-dehydrogenase.
• Reaction:
  1. a 3alpha-hydroxysteroid + NADP⁺ = a 3-oxosteroid + NADPH + H⁺
  2. a 3alpha-hydroxysteroid + NAD⁺ = a 3-oxosteroid + NADH + H⁺

3alpha-hydroxysteroid (Bound ligand (Het Group name = SUZ) matches with 66.67% similarity) + NADP(+) (Bound ligand (Het Group name = NAP) corresponds exactly) = 3-oxosteroid + NADPH + H(+)

3alpha-hydroxysteroid (Bound ligand (Het Group name = SUZ) matches with 66.67% similarity) + NAD(+) (Bound ligand (Het Group name = NAP) matches with 91.67% similarity) = 3-oxosteroid + NADH + H(+)

• Enzyme class 5: E.C.1.1.1.53 - 3alpha(or 20beta)-hydroxysteroid dehydrogenase.
• Reaction: androstan-3alpha,17beta-diol + NAD⁺ = 17beta-hydroxyandrostanone + NADH + H⁺

androstan-3alpha,17beta-diol (Bound ligand (Het Group name = SUZ) matches with 70.37% similarity) + NAD(+) (Bound ligand (Het Group name = NAP) matches with 91.67% similarity) = 17beta-hydroxyandrostanone + NADH + H(+)

• Enzyme class 6: E.C.1.1.1.62 - 17beta-estradiol 17-dehydrogenase.
• Reaction:
  1. 17beta-estradiol + NAD⁺ = estrone + NADH + H⁺
  2. 17beta-estradiol + NADP⁺ = estrone + NADPH + H⁺

17beta-estradiol + NAD(+) (Bound ligand (Het Group name = NAP) matches with 91.67% similarity) = estrone (Bound ligand (Het Group name = SUZ) matches with 66.67% similarity) + NADH + H(+)

17beta-estradiol + NADP(+) (Bound ligand (Het Group name = NAP) corresponds exactly) = estrone (Bound ligand (Het Group name = SUZ) matches with 66.67% similarity) + NADPH + H(+)

• Enzyme class 7: E.C.1.3.1.20 - trans-1,2-dihydrobenzene-1,2-diol dehydrogenase.
• Reaction:
  1. (1R,2R)-1,2-dihydrobenzene-1,2-diol + NADP⁺ = catechol + NADPH + H⁺
  2. (1S,2S)-1,2-dihydrobenzene-1,2-diol + NADP⁺ = catechol + NADPH + H⁺

(1R,2R)-1,2-dihydrobenzene-1,2-diol + NADP(+) (Bound ligand (Het Group name = NAP) corresponds exactly) = catechol (Bound ligand (Het Group name = TLA) matches with 50.00% similarity) + NADPH + H(+)

(1S,2S)-1,2-dihydrobenzene-1,2-diol + NADP(+) (Bound ligand (Het Group name = NAP) corresponds exactly) = catechol (Bound ligand (Het Group name = TLA) matches with 50.00% similarity) + NADPH + H(+)

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site